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[摘要]：Thiopurines are effective immuno-suppressants and anticancer agents. However, the long-term use of thiopurines was found to be associated with a significantly increased risk of various types of cancer. To date, the specific mechanism(s) underlying the carcinogenicity associated with thiopurine treatment remain(s) unclear. Herein, we constructed duplex pTGFP-Hha10 shuttle vectors carrying a 6-thloguanine ((S)G) or S-6-methylthioguanine (S(6)mG) at a unique site and allowed the vectors to propagate in three different human cell lines. Analysis of the replication products revealed that although neither thlonucleoside blocked considerably DNA replication in any of the human cell lines, both (S)G and S(6)mG were mutagenic, resulting In G -> A mutation at frequencies of similar to 8% and similar to 39%, respectively. Consistent with what was found from our previous study in E. coli cells, our data demonstrated that the mutagenic properties of (S)G and S(6)mG provided significant evidence for mutation induction as a potential carcinogenic mechanism associated with chronic thlopurine intervention. |
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